Testing the Combination of an Anti-cancer Drug, Iadademstat, With Other Anti-cancer Drugs (Atezolizumab or Durvalumab) at Improving Outcomes for Small Cell Lung Cancer
Start Date
4/8/2025
Completion Date
7/25/2029
Summary
This phase I/II trial tests the safety, side effects, and best dose of iadademstat when given together with atezolizumab or durvalumab, and studies the effect of the combination in treating patients with small cell lung cancer that has spread outside of the lung in which it began or to other parts of the body (extensive stage) who initially received standard of care chemotherapy and immunotherapy. Iadademstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab or durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding iadademstat to either atezolizumab or durvalumab may be able to stabilize cancer for longer than atezolizumab or durvalumab alone in treating patients with extensive stage small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVE: I. To compare the progression-free survival (PFS) between the combination of iadademstat plus immune checkpoint inhibitor (ICI) versus ICI maintenance alone. SECONDARY OBJECTIVES: I. To compare objective response rate (ORR) and overall survival (OS) between treatment arms. II. To evaluate the safety of combination iadademstat plus ICI. EXPLORATORY OBJECTIVES: I. To assess whether detection of circulating tumor deoxyribonucleic acid (DNA) (ctDNA) minimal residual disease correlates with disease progression. II. To assess whether iadademstat impacts the correlation of ICI (atezolizumab or durvalumab) baseline and time varying clearance with clinical outcomes (PFS and OS) and the presence of cachexia. III. To explore exposure response relationships of iadademstat in combination with ICIs. IV. To characterize changes to small cell lung cancer (SCLC) subtype throughout treatment. OUTLINE: This is a phase I dose-escalation study of iadademstat in combination with atezolizumab and durvalumab followed by a randomized phase II study. PHASE I: Patients receive iadademstat orally (PO) on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab intravenously (IV) over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 arms. ARM I: Patients receive iadademstat PO on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. All patients also undergo multi-gated acquisition (MUGA) or echocardiogram (ECHO), brain magnetic resonance imaging (MRI) or brain computed tomography (CT) during screening, and CT scans and blood and urine sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study. After completion of study treatment, patients are followed up every 3 months for up to 12 months.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Atezolizumab
Biopsy Procedure
Biospecimen Collection
Computed Tomography
Durvalumab
Echocardiography Test
Iadademstat
Magnetic Resonance Imaging
Multigated Acquisition Scan
Conditions
Locations
City of Hope Comprehensive Cancer Center
Duarte, California 91010
United States
City of Hope at Irvine Lennar
Irvine, California 92618
United States
UC San Diego Moores Cancer Center
La Jolla, California 92093
United States
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
Smilow Cancer Hospital Care Center at Saint Francis
Hartford, Connecticut 06105
United States
Yale University
New Haven, Connecticut 06520
United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut 06473
United States
Smilow Cancer Hospital Care Center at Long Ridge
Stamford, Connecticut 06902
United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut 06611
United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia 20007
United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida 32610
United States
Moffitt Cancer Center
Tampa, Florida 33612
United States
Emory University Hospital Midtown
Atlanta, Georgia 30308
United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
United States
Emory Saint Joseph's Hospital
Atlanta, Georgia 30342
United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637
United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois 60451
United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois 60462
United States
UChicago Medicine Northwest Indiana
Crown Point, Indiana 46307
United States
University of Kansas Clinical Research Center
Fairway, Kansas 66205
United States
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas 66211
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland 21201
United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland 21287
United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey 07920
United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey 07748
United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey 07645
United States
Memorial Sloan Kettering Commack
Commack, New York 11725
United States
Memorial Sloan Kettering Westchester
Harrison, New York 10604
United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Memorial Sloan Kettering Nassau
Uniondale, New York 11553
United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina 28203
United States
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina 28025
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina 27157
United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio 45219
United States
Case Western Reserve University
Cleveland, Ohio 44106
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio 45069
United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States